The innate immune response is the first line of defense against microbial pathogens such as viruses, bacteria, fungi, and protozoa. A critical component of the innate immune response is the NFκB family of transcription factors. See e.g., Dev, A. et al., Curr. Top. Microbiol. Immunol. 2011, 34: 115-143; Li, Q. & Verma, I. M., Nature Rev. Immunol. 2002, 2:725-734). The Toll-like receptors (TLRs) are critical components of the innate immune system that regulate NFκB activation. In general, the TLRs recognize macromolecules that are associated with pathogens and with cell stress. These pathogen-associated molecular patterns (PAMPs) and their corresponding TLRs include: lipopeptides (TLR2), double-stranded RNA (TLR3), lipopolysaccharide (LPS) (TLR4) (Fang, H. et al., J. Biol. Chem. 2011, 286:30393-30400), bacterial flagellin (TLR5), guanine and uridine-rich single-stranded RNA (TLR7, 8), and hypo-methylated CpG rich DNA (TLR9) (Hemmi, H. et al., Nature 2000, 408:740-745) Innate immune cells use pattern recognition receptors (PRRs) such as TLRs to promote a rapid response to perceived threats before pathogen-specific adaptive immunity can be established. Indeed, this rapid response, involving multiple components of the innate immune system, has been recognized to guide the type of adaptive immune response that is most effective for the specific pathogenic threat.
Provided herein, inter alia, are compounds and methods useful in modulating innate immune responses.